Release in platelet activating factor (PAF) from basophils has been implicated directly in the pathogenesis of systemic vascular injury in experimental animals involving cardiovascular and pulmonary dysfunction and damage, blood coagulopathy, and acute and chronic inflammatory injury. To date however, the structure of this important mediator in unknown and its presence in man has been reported in a number of laboratories, but as yet, has not been documented adequately. We propose an extensive, multidisciplinary approach for determination of the structure and function of PAF in rabbit and man. Rabbit RAF will be prepared, purified, characterized chemically and if practical synthesized at The University of Texas Health Science Center at San Antonio (UTHSCSA), Texas. Experiments at the National Jewish Hospital and Research Center, Denver, Colorado, will be directed to detection and preparation of human PAF with subsequent chemical characterization at the UTHSCSA. Concurrently we propose to examine the mechanisms of PAF release from basophils, its origin within the cell, and its possible release from other cells such as the macrophage. The effects of PAF on platelets and neutrophils will be studied to determine its role in inducing aggregation, secretion, synthesis of prostaglandins and their intermediates, production of oxygen radicals, and generation of procoagulant activity. The presence and nature of naturally occuring PAF inhibitors also will be sought and finally its presence and biological activity in vivo will be examined. Methods will be devised for detection and hopefully measurement to PAF release in man, and the effects of PAF administration on cardiopulmonary changes, coagulation and blood cell alterations will be assessed in rabbits. These studies are directed towards a greater understanding of the mediation process which may contribute to the pathogenesis of various collagen vascular and allergic diseases, including atherosclerosis.